The ability to establish bonding between biological tissues has long been a goal of biomedical researchers. Attempts to provide desired adhesion through mechanical bonding have proven to be neither convenient nor permanent. For this reason, much attention was devoted to developing synthetic polymers as biomedical adhesives. Such materials, however, have been observed to induce inflammatory tissue reactions. Moreover, the ability of these materials to establish permanent bonding under physiological conditions has not been fully realized.
The known toxicity associated with synthetic adhesives has led investigations towards a development of biologically derived adhesives as bonding materials. Among such adhesives, fibrin based glues have commanded considerable attention. Commercial fibrin tissue adhesives are derived from human plasma and, therefore, pose potential health risks such as adverse immunogenic reactions and transmission of infectious agents. Moreover, the bond strength imparted by such adhesives is relatively weak compared to collagen adhesives.
Collagen, the major connective tissue protein in animals, possesses numerous characteristics not seen in synthetic polymers. Characteristics of collagen often cited include good compatibility with living tissue, promotion of cell growth, and absorption and assimilation of implantations. Natural collagen fibers, however, are not very useful in their native form due to intermolecular crosslinking, insolubility, rigid triple-helical structure, and immunogenicity.
Various methods and materials have been proposed for modifying collagen to render it more suitable as a biomedical adhesive. "In many instances, the prior modified collagen-based adhesives suffer from various deficiencies which include crosslinking/polymerization reactions that generate exothermic heat, long reaction times, and reactions that are inoperative in the presence of oxygen and physiological pH ranges. Moreover, many of the prior art modified collagen-based adhesives contain toxic materials, hence rendering them unsuitable for biomedical use."
Another problem with collagen and other protein-based adhesives is the ability to form bond strengths and film strengths sufficient for the various uses to which such adhesives may be applicable. For example, U.S. Pat. No. 3,438,374 discloses a general matrix as a bioadhesive. Although the material was useful in some applications, the material did not work very well or failed in applications where the material was subjected to substantial pressures or was used to fill a substantial gap in tissue (as opposed to adhering two pieces of tissue together). For example, the adhesive was found not to be effective in sealing divided bronchial stumps (which is characterized by large gaps in tissue) and also was not effective in sealing blood vessels (which involve elevated fluid flow at high pressures).
A more recent advance in the field is the use of collagen monomers derivatized with an acylating agent or a sulphonating agent and polymerized with an appropriate polymerization initiator such as a chemical oxidant, ultraviolet irradiation, a suitable oxidative enzyme or atmospheric oxygen. These materials were shown to be biologically compatible, and their use was proposed for a number of biological applications. In particular, it was disclosed that these materials be used as adhesives to hold two tissues together or to hold a synthetic lenticule to an eye. They also were disclosed as useful in the formation of flexible films which could be used as a lap following surgery to prevent adhesion, as a synthetic tympanic membrane, as a substitute facial tissue, and as a wound dressing component. It was stated that the adhesive also may be used to seal an incision following cataract removal. The material was not proposed for use in sealing fluid leaks in a tissue that is a conduit and in particular in a tissue that is exposed to pulsating and elevated pressures in situ.